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Supplementary Figure 8 from The Impact of Inherited Genetic Variation on DNA Methylation in Prostate Cancer and Benign Tissues of African American and European American Men

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posted on 2024-04-03, 07:21 authored by Dayana Delgado, Marc Gillard, Lin Tong, Kathryn Demanelis, Meritxell Oliva, Kevin J. Gleason, Meytal Chernoff, Lin Chen, Gladell P. Paner, Donald Vander Griend, Brandon L. Pierce

Supplementary Figure 8 shows the regional association plots for the AA meQTL and PCa GWAS signal in the MLPH region

Funding

U.S. Department of Defense (DOD)

National Institute of Environmental Health Sciences (NIEHS)

United States Department of Health and Human Services

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Susan G. Komen (SGK)

National Institute on Aging (NIA)

United States Department of Health and Human Services

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National Institute of General Medical Sciences (NIGMS)

United States Department of Health and Human Services

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ARTICLE ABSTRACT

American men of African ancestry (AA) have higher prostate cancer incidence and mortality rates compared with American men of European ancestry (EA). Differences in genetic susceptibility mechanisms may contribute to this disparity. To gain insights into the regulatory mechanisms of prostate cancer susceptibility variants, we tested the association between SNPs and DNA methylation (DNAm) at nearby CpG sites across the genome in benign and cancer prostate tissue from 74 AA and 74 EA men. Genome-wide SNP data (from benign tissue) and DNAm were generated using Illumina arrays. Among AA men, we identified 6,298 and 2,641 cis-methylation QTLs (meQTL; FDR of 0.05) in benign and tumor tissue, respectively, with 6,960 and 1,700 detected in EA men. We leveraged genome-wide association study (GWAS) summary statistics to identify previously reported prostate cancer GWAS signals likely to share a common causal variant with a detected meQTL. We identified nine GWAS-meQTL pairs with strong evidence of colocalization (four in EA benign, three in EA tumor, two in AA benign, and three in AA tumor). Among these colocalized GWAS-meQTL pairs, we identified colocalizing expression quantitative trait loci (eQTL) impacting four eGenes with known roles in tumorigenesis. These findings highlight epigenetic regulatory mechanisms by which prostate cancer-risk SNPs can modify local DNAm and/or gene expression in prostate tissue. Overall, our findings showed general consistency in the meQTL landscape of AA and EA men, but meQTLs often differ by tissue type (normal vs. cancer). Ancestry-based linkage disequilibrium differences and lack of AA representation in GWAS decrease statistical power to detect colocalization for some regions.

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